The synthesis and properties of Gla- and Phe-containing analogues of cyclic RGD pentapeptides

Cyclopentapeptides containing the Arg-Gly-Asp motif have been synthesised u sing solid-phase assembly of side-chain-protected linear precursors, follow ed by solution-phase cyclisation. The replacement of the Asp residue by gam ma-carboxyglutamic acid (Gla) is a novel feature which gives rise to an ana logue which inhibits cell adhesion, yet its congeners do not show activity in binding assays with recombinant integrin receptors. NMR techniques suppo rt a beta/gamma-turn conformation in most of the analogues.